These studies will be a continuation of several already under way and several new projects stemming in part from experience this principal investigator had during his sabbatical year with Professor H. A. Krebs. It has been demonstrated that there is an erythrocyte transport defect in certain patients with metastatic malignancy. An effort will be made to find an inhibitor of transport from extracts of tumors from these patients. The number of ouabain binding sites on the erythrocytes of patients with uremia will be examined. It will be determined not only what the number of sites may be, but the kinetics of binding in these red cells compared with control subjects and the influence on the number and the kinetics of binding with respect to the red cell sodium concentration. In addition, the metabolic pathways of the erythrocyte in patients with uremia with and without elevated concentrations of sodium will be studied and compared with control red cells. The question of the level of 2-3 DPG in the erythrocytes of patients with cirrhosis of the liver and hypophosphatemia will be investigated. The hypothesis is that the hypophosphatemia is accompanied by depressed levels of 2-3 DPG which in turn modify the oxygen dissociation curve which leads to increased respiratory activity and the respiratory alkalosis so common in these patients. The principal investigator learned the techniques of hind limb perfusion and isolated liver perfusion while in Professors Krebs' laboratory. These techniques have not been employed to date to study the influence of the ionic environment on the rates and directions of a whole variety of metabolic pathways. The use of these techniques may very well shed considerable light on the nature of the abnormalities accompanying electrolyte disturbances.